A 11‐Steps Total Synthesis of Magellanine through a Gold(I)‐Catalyzed Dehydro Diels–Alder Reaction

Abstract

We have developed an innovative strategy for the formation of angular carbocycles via a gold(I)-catalyzed dehydro Diels-Alder reaction. This transformation provides rapid access to a variety of complex angular cores in excellent diastereoselectivities and high yields. The usefulness of this Au -catalyzed cycloaddition was further demonstrated by accomplishing a 11-steps total synthesis of (±)-magellanine.

Twelve-Step Asymmetric Synthesis of (−)-Nodulisporic Acid C

“…The key transforms in our retrosynthetic analysis of nodulisporic acid C ( 3 ) included a late-stage indole assembly to form the C14–C15 and N1–C2 bonds and two polycyclization events to access the terpenoid and indenopyran motifs. We envisioned a radical-polar crossover cascade initiated by a chemoselective 20,21 hydrogen atom transfer (HAT) 22–24 to construct the C4–C9 and C8–C7 bonds of the decalin fragment and a gold-catalyzed cycloisomerization 25 to construct the C18–C23 and O21–C22 bonds of the dihydropyran fragment. We previously discovered a diastereoselective polycyclization related to the proposed HAT-initiated cascade, which relied on a transient lactolization event to control the relative orientation of the C3–C4 vicinal quaternary stereocenters.…”

Development of New Gold (I)‐Catalyzed Carbocyclizations and their Applications in the Synthesis of Natural Products

“…Angular scaffolds such as 29 are embedded in various natural terpenes and alkaloids . We demonstrated the practicality of this method by accomplishing the total synthesis of (±)‐magellanine in a short and efficient manner …”

Empowering Synthesis of Complex Natural Products

“…With the increasing levels of sophistication in catalytic systems, new bond disconnections can be envisioned to construct challenging stereocenters. This is epitomized by the recent developments in gold‐catalyzed carbocyclizations, particularly Barriault's dehydro‐Diels–Alder reaction, which can set quaternary stereocenters . With few methods for the generation of quaternary stereocenters, they often become the greatest hurdles in the synthesis of natural products.…”